Abstract

The vancomycin–ristocetin family of glycopeptides is a subclass of linear sugar-containing peptides composed of seven amino acids cross-linked to generate a specific stereochemical configuration. This configuration forms the basis of a particular mechanism of action, eg, complexation with the D-alanyl-D-alanine terminus of bacterial cell wall components. The term dalbaheptide, from D-al (anyl-D-alanine)b(inding)a(ntibiotics) having hept(apept)ide structure, has been proposed to distinguish them within the larger and diverse groups of glycopeptide antibiotics. About 40 different naturally produced dalbaheptides have been reported. Among them, vancomycin and teicoplanin are used clinically as a result of high activity against gram-positive pathogens such as many coagulase-negative Staphylococci (CNS), corynebacteria, Clostridium difficile, multiresistant Staphylococcus aureus, and highly gentamicin-resistant Enterococci which are refractory to established drugs. Eremomycin is under clinical evaluation. Many patents claim feed-utilization efficiency increase and growth promotion in domestic animals for several dalbaheptides but only avoparcin (Avotan) is commercially used. Knowledge of the mechanism of action and investigations on the physicochemical characteristics has stimulated the transformation of natural antibiotics into new dalbaheptide derivatives using both chemical and biosynthetic modification. All the dalbaheptides are produced by strains belonging to the order of Actinomycetales. Dalbaheptides are produced by submerged fermentation. Pure dalbaheptides are obtained as colorless or whitish amorphous powders that usually retain water and solvents. Dalbaheptides are generally water-soluble. Teicoplanin can be obtained as an internal salt or as a partial monoalkaline (sodium) salt. Other dalbaheptides are obtained as acidic salts. Dalbaheptides are levorotatory. The basis of the antibacterial action of dalbaheptides is the ability to form a complex with the terminal D-Ala-D-Ala residues of growing peptidoglycan chains, thus preventing transglycosylation, eg, chain elongation, and transpeptidation, eg, cross-linking. The consequent defective cell wall stops bacterial growth and eventually leads to cell death. Only three dalbaheptides are commercialized: vancomycin and teicoplanin for human health, and avoparcin for animal usage. Vancomycin and teicoplanin as formulated drugs are lyophilized powders to be reconstituted with sterile water for injection.